Dialkylaminoalkyl esters of phenyl substituted dihydroxybenzoic acids



DIALKYLAMINOALKYL ESTERS OF PHENYL SUB- STITUTED DHIYDROXYBENZOIC ACIDSFloyd L. Beman, Midland, Mich., assignor to The Dow Chemical Company,Midland, l\ Iich., a corporation of Delaware No Drawing. ApplicationJuly 9, 1953, Serial No. 367,103

7 Claims. (Cl. 260473) lococcus aureus.

The new ester compounds may be prepared by reacting a phenyl substituteddihydroxybenzoic acid of the formula with a dialkylamino haloalkane ofthe formula R Cl(CnH2n)N The reaction is usually conducted in thepresence of an organic solvent such as isopropanol and takes placesmoothly at temperatures in excess of about 60 C. In a convenient modeof operation, the reaction may be During the cooling a dialkylaminoalkylphenyl-dihydroxybenzoic acid hydrochloride precipitates as a crystallinesolid. The latter may be punfied by recrystallization from variousorganic solvents.

nited States Patent 0 The free esters can be recovered by treating anaqueous solution of the hydrochloride with an alkali metal hy- Thelatter may be purified by recrystallization from alcohol or other suit-Lower alkyl as used in this specification and appended claims isintended to include all aliphatic groups having from 1 to 4 carbonatoms, inclusive, e. g. methyl ethyl; propyl; isopropyl; butyl;secondarybutyl; and tertiary .utyl. The carbon chain of the alkylenegroup, -Cn figuration. Representative groups include ethylene;propylene; trimethylene; butylene; l-methy -trimethylene; 2-methyl-trimethylene; and tetramethylene. Representative basic alkylesters, which among others, are within the scope of the invention,include ,B-diisopropylaminosecondarybutyl3-phenyl-2,S-dihydroxybenzoatc; fi-methyl-ethylaminoethyl4-phenyl-2,S-dihydroxybenzoate; butyl-methylaminopropylS-phenyl-Z,3-dihydroxybenz0- ate; -dibutylaminobutyl3-phenyl-2,S-dihydroxybenzoate and fl-diethylaminoethyl6-phenyl-2,S-dihydroxybenzoate.

The following examples are givento illustrate one manner which may beused to prepare the compounds of limiting.

36.8 grams (0.16 mole) of 4-phenyl-2,5-dihydroxybenzolc acid wasdissolved in milliliters of ISOPIO- under reflux. The solvent was thenremoved by evaporation to obtain a fi-diethylaminoethyl4-phenyl-2,5-dihy- Example 2. 3-Dimethylaminoisopropyl 6-phenyl-2,5-dz'hydroxybenzoate hydrochloride 0.4 mole quantities of6-phenyl-2,S-dihydroxybenzoic acid and dimethylarnino-Z-chloropropaneand 300 milliliters of isopropanol are mixed together and thereafterheated for 6 hours at the boiling temperature of the mix- The solventalcohol is then removed by evaporation to obtain aB-dimethylaminoisopropyl 6-phenyl-2,S-dihydroxybenzoate \hydrochlorideproduct as a crystalline residue.

Example 3. ;9-Diethylamz'noethyl 3-phenyl-2,5-dihydroxybenzoatehydrochloride The resulting mixture was thereafter heated for abouthours at the boiling temperature and under reflux. Following the heatingperiod, the solvent was separated from the reaction mixture byevaporation to obtain a fi-diethylaminoethyl3-phenyl-2,5-dihydroxybenzoate hydrochloride product 'as. a crystallineresidue. The latter was recrystallized from isopropanol and found tohave a melting point of 187.5 -189 C.

Example 4.--;3-Diisopropylaminoethyl 3-phenyl-2,S dihydroxybenzoatehydrochloride 0.2 mole quantities of 3-phenyl-2,5-dihydroxybenzoic acidand diisopropylamino-2-chloroethane and 225 milliliters of isopropanolare mixed together and thereafter heated for about 5 hours at theboiling temperature of the mixture and under reflux. The alcohol solventis then removed by evaporation to obtain a .fi-diisopropylaminoethyl3phenyl-2,S-dihydroxybenzoate hydrochloride as a crystalline residue.

Example 5.-fl-Diethylaminoetlzyl 5-phenyl-2,3-dihydroxybenzoatehydrochloride Example 6.-fi Diethylaminoethyl4-phenyl-2,5-dihydroxybenzoate Five milliliters of normal aqueous sodiumhydroxide was added portionwise to 2 grams of p-diethylamino-ethyl4-phenyl-2,5-dihydroxybenzoate hydrochloride dissolved in 100milliliters of water. Following the addition, a B- diethylaminoethyl4-ph'enyl-2,5-dihydroxybenzoate product crystallized in the mixture andwas extracted therefrom with benzene. The benzene was then removed byevaporation and the residue dried and found to melt at 98-101 C.

Example 7.-'-l8-Diethylaminoethyl 4-phenyl-2,5-dihy droxybenzoa'tesulfate 1.6 milliliters of normal sulfuric acid was added portionwise to0.5 gram of p diethylaminoethyl 4-phenyl- 2,5-dihydroxybenzoatedissolved in a mixture of 100 milliliters of methanol and SOmilliIitersof isopropanol. The solvent was then removed by evaporation to obtain adiethylaminoethyl 4-phenyl-'2,5-dihydroxybenzoate sulfate product as acrystalline residue. The latter had a melting point of 113114 C.

The phenyl substituted dihydroxybenzloic acids, employed as startingmaterials as previously described, may be prepared by hydrolyz'ng asuitable halogenated phenyl 2-hydroxybenzoic acid. The hydrolysis iscarried out in an aqueous alkaline medium and preferably in an aqueoussolution of an alkali metal hydroxide. The reaction takes place smoothlyat temperatures of from 50 to 180 C. Upon completion of the hydrolysis,the reaction mixture is acidified with a mineral acid, the desiredphenyl substituted dihydroxybenzoic acid product precipitating as acrystalline solid. The latter compounds and methods for their productionconstitute the subject matter of my copending application, Serial No.367,102, filed concurrently herewith.

The halogenated phenyl-Z-hydroxybenzoic acids as described above rnay beprepared by halogenating a suitable phenyl substituted Z-hydroxybenzoicacid in glacial acetic acid as reaction medium. The halogenation takesplace smoothly at temperatures of from about to C. In carrying out thereaction, bromine, chlorine, or iodine chloride is contacted portionwisewith the phenyl 2-hydroxybenzoic acid dissolved in acetic acid and underconditions of elevated temperature in the reaction vessel. Uponcompletion of the reaction, the mixture may be diluted with water toprecipitate the halogenated phenyl Z-hydroxybenzoic acid product as acrystalline solid. These compounds and methods for their production aredisclosed in a copending application, Serial No. 327,455, filed December22, 1952.

I claim:

1. A compound selected from the group consisting of (a) esters havingthe formula Z O R EO-iJ-O-Gdin-b/ x '4 \R wherein n represents aninteger from 2 to 4, inclusive, each R represents a lower alkyl radicalcontaining from 1 to 4 carbon atoms, inclusive, X represents a phenylradical, Y represents hydroxyl and Z represents hydroxyl which is metato the carboxy group and is para to Y when X is meta to Y, and (-b) theacid addition salts thereof.

2. Acid addition salts of esters having the formula from 2 to 4,inclusive,

3-phenyl-2,S-dihydroxybenzo- 4-pheny1-2,S-dihydroxybenzo-5-phenyl-2,3-dihydroxybenzot 4-phenyl-2,S-dihydroxybenzoa 7.fl-Diethylaminoethyl ate sulfate.

4-phenyl-2,5-dihydroxybenzo- References Cited in the file of this patentUNITED STATES PATENTS Christiansen 'et al Oct. 16, 1934 Sahyun Apr. 29,1952

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF (A) ESTERS HAVING THE FORMULA 